This invention relates to apparatus for dispensing a predetermined volume of a liquid, comprising a source or reservoir for the liquid, a channel provided with an outlet for conveying the liquid from the source or reservoir to the outlet, and means for generating pulse of gas, the apparatus being constructed and arranged such that in use said pulse of gas causes a predetermined volume of liquid to be ejected from said outlet. It relates particularly, though not exclusively, to apparatus for dispensing biochemical reagents. Dispensers for dispensing biochemical reagents can provide a non-contact means for dispensing small volumes of a liquid, commonly in the range 0.1 nl to 100 xcexcl. Dispensers based on conventional ink jet printer technologies are most generally applied for dispensing volumes in the 0.5 nl to 10 nl range.
Accurate and rapid dispensing of reagents is very important in high-throughput applications. Dispensers which may be used for automated dispensing of reagents and solutions for synthesis, including combinatorial chemistry, and for chemical and biochemical testing are hereinafter referred to as reagent dispensers.
A reagent dispenser is described in an article entitled xe2x80x9cCharacterisation of an ink-jet chemical micro dispenser for combinatorial library synthesisxe2x80x9d, which was published in Analytical Chemistry, Vol. 69, No. 4, February 1997, at page 543. The dispenser is complex and requires three different types of solenoid valves to control the delivery of a pressurised gas which dispenses reagent.
Another device is described in published International Patent Application WO 9715394. This device consists of a multi-well plate where the wells have a large opening at the top and a small opening in the base through which a liquid is ejected when a pressure pulse is applied to the top surface of the liquid.
According to a first aspect of the present invention there is provided apparatus as defined in claims 1-10. According to a second aspect of the invention there is provided a liquid handling system as defined in claims 11-15.
Known dispensers have difficulty in dispensing sufficiently small volumes of liquid to meet current and future requirements. Moreover, the liquids which must be dispensed in biochemical applications can vary considerably in viscosity and may be sensitive to heat, pressure and/or liquid shear forces, this renders the use of conventional ink-jet dispensing techniques extremely difficult.
Cross contamination of dispensing mechanisms by different reagent liquids is another problem in the use of dispensers in chemical and biological synthesis and testing. It is desirable that liquid handling components should be cheap and therefore disposable to reduce the need for expensive and possibly unreliable washing procedures. Known ink-jet mechanism based systems involve relatively complex components contacting the dispensed liquid, and are generally too expensive to be treated as disposable components.
The present invention can provide a simple structure for rapidly delivering liquid to one or more collecting sites where reproducible liquid droplets may be repeatedly generated without contact to the collecting sites, and where the droplet ejecting force is provided by a separate air or gas stream control. This allows the actuating element to be confined to the air or gas stream, avoiding contact with the dispensed liquid and possible contamination. The simple structure enables manufacture at low cost.
The performance of conventional ink-jet printer mechanisms, in which the droplet actuating mechanism contacts or is immersed in the liquid to be dispersed, is grossly affected by the viscosity of that liquid. The present invention provides a means whereby the actuating mechanism is not directly in contact or affected by the liquid, and can be widely adjusted to cope with various liquid viscosities. The simple geometry whereby a slug of liquid is confined between orifices in thin planar sheets will result in ejection forces which are not strongly dependant on liquid viscosity.
A common cause of failure in reagent dispenser delivery systems is spattering of chemical solvents from the base of shallow wells (typically arranged in an array on a tray) into which reagent is dispensed. The result is that liquid spills into adjacent wells. This has limited the performance of known dispensers.
The invention provides apparatus which can be constructed to dispense liquid volumes selected in the range, for example, of 1 nl to 1 xcexcl for the range of solution and liquid viscosity commonly encountered in biochemistry, with good volumetric control and adequate repetition rate.